Accepted Manuscript The Role of Radiosurgery for Infratentorial Arteriovenous Malformations Aditya Iyer, M.D. Steven Chang, M.D PII:

S1878-8750(14)00461-6

DOI:

10.1016/j.wneu.2014.05.002

Reference:

WNEU 2357

To appear in:

World Neurosurgery

Received Date: 13 March 2014 Accepted Date: 2 May 2014

Please cite this article as: Iyer A, Chang S, The Role of Radiosurgery for Infratentorial Arteriovenous Malformations, World Neurosurgery (2014), doi: 10.1016/j.wneu.2014.05.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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The Role of Radiosurgery for Infratentorial Arteriovenous Malformations

Aditya Iyer, M.D., Steven Chang, M.D.

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Address for Correspondence: Steven Chang, MD Department of Neurological Surgery Stanford University 300 Pasteur Dr. Stanford, CA 94305

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Departments of Neurological Surgery, Stanford University

Key Words: stereotactic radiosurgery, Cyberknife, stroke, arteriovenous malformations, infratentorial, posterior fossa

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Running title: Radiosurgery for Infratentorial Arteriovenous Malformations

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Over the past three decades, radiosurgery has become an important modality in the management of arteriovenous malformations (AVMs) of the brain and spinal cord. Infratentorial AVMs comprise approximately 5-15% of all intracranial AVMs and among those, 60% are found

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entirely within the cerebellum, 20% in the brainstem and 20% in both [1]. While supratentorial AVMs generally present with seizures, headaches, or progressive neurologic changes,

infratentorial AVMs predominantly present with hemorrhage and are generally more devastating to patients [8, 10]. Prior bleeding is significantly associated with hemorrhage of both

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supratentorial and infratentorial AVMs, with a reported relative risk of up to 9.0 [11] and a 9.4%

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pretreatment rehemorrhage rate in the posterior fossa in our Stanford series (compared to 8.4% for unruptured AVMs) [7]. Hemorrhage is more common within the cerebellum than the brainstem, with a mortality of 60% [3, 5]. Though brainstem AVMs have a lower rate of hemorrhage [12], they have considerably greater morbidity [3]. Despite these facts, the majority

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of studies on posterior fossa AVMs do not distinguish between cerebellar and brainstem location. Several scoring systems have been developed to predict the likelihood complete obliteration for cerebellar AVMs [15]. The Pollock-Flickinger score [13, 14], which has been a useful tool to

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prognosticate radiosurgical outcomes for supratentorial AVMs, does not predict outcomes for infratentorial AVMs [2, 6]. Differences in angioarchitectural properties and flow dynamics

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within the posterior-fossa, affect both the natural history and post-treatment obliteration of infratentorial AVMs [16]. Hence infratentorial AVMs remain distinct and challenging clinical entities.

The imminent risk of herniation from hemorrhage within the posterior fossa, in addition to advances in microsurgical techniques, have made surgical resection with or without adjuvant

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embolization the most common treatment option. However, the morbidity and mortality rates from surgical resection of infratentorial AVMs are approximately 14% and 20% respectively [1, 4]. At our own institution we generally wait at least one month after initial hemorrhage before

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proceeding with surgical resection AVM to allow for hemodynamic stability and neurological recovery, unless emergent surgery is necessary if the hemorrhage is causing mass effect and/or neurologic deterioration. Even in cases of hemorrhage evacuation, we typically do not address

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the AVM in the emergent setting. Our series reported an overall morbidity and mortality rate of 18.8% for infratentorial AVMs, with no significant outcome difference between radiosurgery,

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embolization, and surgical resection as the primary treatment modality [7]. The latency period between radiosurgery and complete obliteration, in which patients are not entirely protected from hemorrhage, ranges from 3-5 years [9] and the hemorrhage rate during this period is approximately 2% [2]. Therefore careful selection of patients to undergo radiosurgery for

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posterior fossa AVMs is necessary.

In this issue of WORLD NEUROSURGERY, Ding et al. describe post-radiosurgery outcomes

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for 60 patients with cerebellar AVMs. Given the limited data on infratentorial AVMs treated with radiosurgery, this is an important study that is well powered to demonstrate the utility of

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radiosurgery for cerebellar AVMs. Ding et al. report a median radiographic follow up of 39 months, which is sufficiently long to account for delayed adverse radiation effects and hemorrhage during the post-radiosurgical latency period. However, because patients with less than two years of radiographic follow up were excluded, fatal hemorrhages and adverse radiation effects are not fully accounted for which, the authors acknowledge as a limitation. Additionally given that infratentorial AVMs were more likely to be hemorrhagic in this series, it is not

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entirely possible to conclude that infratentorial (which in this paper is exclusively cerebellar) location does not affect radiosurgical outcomes. Prior hemorrhage likely confounds outcomes,

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and is not evenly distributed between infratentorial and supratentorial AVMs.

Similar to Bowden et al. [2], Ding et al report an obliteration rate of over 70% following

radiosurgery. Our own series demonstrated an overall obliteration rate of 28.6% for patients who

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underwent one to two Cyberknife treatments alone, compared to 61.8% who underwent

multimodality treatment [7]. Both Ding et al. and Bowden et al. [2] found that smaller size and

predict better outcomes as well.

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no prior embolization were positive prognostic factors, whereas Ding et al. found younger age to

AVMs within the posterior fossa can be life threatening and require complex clinical decision-

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making. As technology continues to improve, along with surgical resection and endovascular therapy, radiosurgery plays an important role in the multimodality management of these difficult to treat lesions. More studies with longer-term follow up are required to better demonstrate the

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effect of radiosurgery on infratentorial AVMs. Our recommendation is that small, unruptured AVMs within the posterior fossa, as well as those that are not easily amenable to surgical

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resection, such as those in the brainstem, may be managed with radiosurgery alone.

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The role of radiosurgery for infratentorial arteriovenous malformations.

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